Quercetin-containing compositions

ABSTRACT

This invention relates to a composition containing quercetin, vitamin B3, and vitamin C. Also disclosed is a method of using the composition for enhancing physical or mental performance or treating various diseases or disorders.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.11/778,234, filed on Jul. 16, 2007, now U.S. Pat. No. 7,745,486 whichclaims priority from U.S. Provisional Patent Application No. 60/807,601,filed Jul. 17, 2006, U.S. Provisional Patent Application No. 60/807,694,filed Jul. 18, 2006, U.S. Provisional Patent Application No. 60/900,626,filed Feb. 8, 2007, U.S. Provisional Patent Application No. 60/911,747,filed Apr. 13, 2007, and U.S. Provisional Patent Application No.60/913,164, filed Apr. 20, 2007. Contents of these prior applicationsare incorporated herein by reference in their entireties.

BACKGROUND

It is known that certain natural antioxidants, such as quercetin,inhibit both acute and chronic phases of free-radical induced diseases.Further, some natural antioxidants exhibit synergy in their reactionswith biologically relevant oxygen species, e.g., hydroxyl radicals,superoxides, oxysulfurs, sulfur dioxide, and nitrogen dioxide.

SUMMARY

In one aspect, the invention features a composition containingquercetin, vitamin B3, and vitamin C, in which a weight ratio betweenquercetin, vitamin B3, and vitamin C is 1:0.02-1:0.2-2.5.

The composition, either in dry form (e.g., powder or tablet) or inliquid form (e.g., beverage or syrup), can be a dietary supplement or apharmaceutical formulation. The dietary supplement or the pharmaceuticalformulation can be in the form of a tablet, a capsule, a soft chew, or agel. The composition can also be a food product. Examples include tea(e.g., a tea drink and the contents of a tea bag), soft drinks, juice(e.g., a fruit extract and a juice drink), milk, coffee, jelly, icecream, yogurt, cookies, cereals, chocolates, and snack bars.

In another aspect, the invention features a composition consistingessentially of quercetin, vitamin B3, and vitamin C. The term“consisting essentially of” used herein limits the composition to thejust-mentioned three ingredients and those that do not materially affectits basic and novel characteristics, i.e., the efficacy in treating oneor more target conditions described herein (e.g., mental fatigue, viralinfection, and tumor). An example of such a composition contains thejust-mentioned three ingredients and a pharmaceutically acceptablecarrier. Another example is a soft chew composition containing the threeingredients and various inactive additives (e.g., excipients,sweeteners, and artificial flavors).

In still another aspect, the invention features a method for enhancingphysical or mental performance. The method includes administering to asubject in need thereof an effective amount of the above-describedcomposition. Examples of improved physical performance include increasedstamina and improved speed, strength, power, endurance, flexibility,agility, balance, focus coordination, reaction time, and fatiguerecovery. Examples of improved mental performance include improvedsharpness, attention span, mental alertness, cognitive functions, and/ormood elevation, and recovery or reduction of depression, anxiety, and/ormental fatigue (e.g., following a high-intensity physical exercise). Byproperly administrating the composition, a subject's physical or mentalperformance can be greatly enhanced without deleterious side effects.

In yet another aspect, the invention features a method for treating adisorder associated with C-reactive protein (e.g., a cardiovasculardisorder) or lowering cholesterol levels by administering to a subjectin need thereof an effective amount of the above-described composition.

In a further aspect, the invention features a method of administering toa subject in need thereof an effective amount of the above-describedcomposition to treat one or more of the following diseases: autoimmunedisease, inflammatory disease, arthritis, tumor, diabetes, sexualdysfunction, chronic constipation, cold, viral and bacterial infection(e.g., upper respiratory tract infection), or neurodegenerative disease(e.g., age-related brain degenerative disease).

Also within the scope of this invention is a composition containing thecomposition described above for use in treating the above-describeddisorders or conditions, and the use of such a composition for themanufacture of a medicament for the just-mentioned treatment.

The details of one or more embodiments of the invention are set forth inthe description below. Other features, objects, and advantages of theinvention will be apparent from the description and from the claims.

DETAILED DESCRIPTION

This invention is based, at least in part, on the unexpected findingsthat a composition containing quercetin, vitamin B3, and vitamin C asactive ingredients exhibits synergistic health benefits, includingenhancing physical or mental performance in a subject, and that, uponoral administration, a combination of quercetin, vitamin B3, and vitaminC results in a significantly higher quercetin concentration in plasmathan quercetin alone. Additional and related surprising observationsinclude that a combination of quercetin, vitamin B3, and vitamin Cmaintains quercetin levels in plasma up to five times those of quercetinalone or a combination of quercetin and vitamin B3; and that acombination of quercetin, vitamin B3, and vitamin C results in aquercetin half life in plasma twice as long as that of quercetin aloneand about one and a half times that of a combination of quercetin andvitamin B3.

The weight ratio between quercetin, vitamin B3, and vitamin C in acomposition of the invention can be 1:0.02-1:0.2-2.5, or any ratio inbetween. For example, the weight ratio can be 1:0.04-0.5:0.3-2.0,1:0.05-0.3:0.4-1.5, 1:0.05-0.2:0.5-1, and 1:0.1-0.2:0.5-1. Preferredratios include about 1:0.02:1, about 1:0.04:1, about 1:0.08:1, about1:0.05:1.5, and about 1:0.16:1. Typically, a subject can beadministered, once or periodically per day, with the composition in anamount that provides 100 mg to 2 g (preferably, 250 mg to 1 g) ofquercetin. The term “quercetin” refers to both quercetin aglycon andquercetin derivatives, e.g., quercetin-3-O-glucoside,quercetin-5-O-glucoside, quercetin-7-O-glucoside,quercetin-9-O-glucoside, quercetin-3-O-rutinoside,quercetin-3-O-[α-rhamnosyl-(1→2)-α-rhamnosyl-(1→6)]-β-glucoside,quercetin-3-O-galactoside, quercetin-7-O-galactoside,quercetin-3-O-rhamnoside, and quercetin-7-O-galactoside. Afterdigestion, quercetin derivatives are converted to quercetin aglycon andother active derivatives, which are absorbed in the body. The quantityof quercetin mentioned above refers to that of quercetin aglycon or thequercetin moiety of a quercetin derivative. Quercetin can be added tothe composition either in a pure form or as an ingredient in a mixture(e.g., a plant extract). Examples of commercially available quercetininclude QU995 (containing 99.5% quercetin) and QU985 (containing 98.5%quercetin) from Quercegen Pharma LLC (Newton, Mass.) and Merck KGaA(Brazil). “Vitamin B3” mentioned herein includes vitamin B3 in itsvarious forms, including niacinamide, nicotinic acid, nicotinamide,inositol hexaniacinate. “Vitamin C” mentioned herein includes vitamin C(i.e., L-ascorbic acid, D-ascorbic acid, or both) and its salts (e.g.,sodium ascorbate).

The composition of this invention can be in various forms. For example,it can be a soft chew composition that includes quercetin, niacinamide,ascorbic acid, sodium ascorbate, sugar, corn syrup, sucralose, soylecithin, corn starch, clycerin, palm oil, xylitol, carrageenan, FD&CYellow #6, FD&C Yellow #5, and natural and/or artificial flavors. Anexemplary serving of this soft chew composition (5.15 g) includes 250 mgof quercetin, 12.9 mg of vitamin B3 (i.e., niacinamide), and 382.8 mgvitamin C (i.e., L-ascorbic acid and sodium ascorbate). A subject cantake one to eight servings (e.g., 4 servings) of this soft chewcomposition daily. The amounts taken can vary depending on, for example,the disorder or condition to be treated and the physical states of thesubject. Another exemplary composition of this soft chew includes 5.25wt % of quercetin, 0.25 wt % of vitamin B3, and 7.81 wt % of vitamin C(i.e., L-ascorbic acid and sodium ascorbate).

The composition of this invention can further contain one or more activeingredients, such as an isoflavone (e.g., genistein or genistin),curcumin, resveratrol, isoquercetin, luteolin, epigallocatechin gallate(EGCG), CoQ10, eicosapentaenoic acid (EPA), and docosahexaenoic acid(DHA). These active ingredients can be added to the composition eitherin a pure form or as a component in a mixture (e.g., an extract from aplant or an animal). A suitable daily dosage of each of theseingredients can vary depending on, for example, the disorder orcondition to be treated and the physical states of the subjects.Exemplary daily dosages of some of these ingredients are: 20-2,500 mg(preferably 250-1,000 mg) of curcumin, 10-1,000 mg (preferably 100-500mg) of resveratrol, 10-1,000 mg (preferably 100-250 mg) of isoquercetin,50-1,000 mg (preferably 100-700 mg) of EGCG, 25-300 mg (preferably50-100 mg) of genistin/genistein, 10-1,000 mg (preferably 100-200 mg) ofluteolin, 50-1,000 mg (preferably 70-500 mg) of EPA, and 50-1,000 mg(preferably 80-700 mg) of DHA. Further, it can be sweetened, ifnecessary, by adding a sweetener such as sorbitol, maltitol,hydrogenated glucose syrup and hydrogenated starch hydrolyzate, highfructose corn syrup, cane sugar, beet sugar, pectin, and sucralose. Thecomposition can also contain amino acids, fatty acids, proteins, fibers,minerals, a flavor enhancer, or a coloring agent. Exemplary amino acidsinclude theanine (e.g., L-theanine) and alanine (e.g., L-alanine).Exemplary fatty acids include omega-3 fatty acids (e.g., linolenicacid), omega-6 fatty acids (e.g., linoleic acid), and omega-9 fattyacids (e.g., oleic acid). Exemplary proteins include plant proteins,such as soy proteins and chia seed proteins. Exemplary fibers includeplant fibers, such as soy fibers and chia seed fibers. These ingredientscan be added in the above-described composition either in a pure form oras a component in a mixture (e.g., an extract from a plant or ananimal).

When the above-described composition is in powder form, it can be usedconveniently to prepare beverage, paste, jelly, capsules, or tablets.Lactose and corn starch are commonly used as diluents for capsules andas carriers for tablets. Lubricating agents, such as magnesium stearate,are typically included in tablets.

The composition of this invention can be a dietary supplement or apharmaceutical formulation. As a dietary supplement, additionalnutrients, such as minerals or amino acids may be included. Thecomposition can also be a food product. As used herein, the term “food”broadly refers to any kinds of liquid and solid/semi-solid materialsthat are used for nourishing humans and animals, for sustaining normalor accelerated growth, or for maintaining stamina or alertness. Examplesof human food products include, but are not limited to, tea-basedbeverages, juice, coffee, milk, jelly, cookies, cereals, chocolates,snack bars, herbal extracts, dairy products (e.g., ice cream, andyogurt), soy bean product (e.g., tofu), and rice products.

The composition of this invention significantly lowers both cholesteroland C-reactive protein levels, and increases the hemoglobin levels, thenumber of reticulocytes, and the mass of red blood cells. For example,it lowers the C-reactive protein levels in both subjects having higherthan normal C-reactive protein levels and subjects having normalC-reactive protein levels. Further, this composition results inincreased mitochondrial biogenesis or retention (e.g., in muscle andbrain cells), reduced mitochondrial DNA damage and loss of mitochondria,or increased cytochrome C levels and citrate synthase activities. Thus,it is useful in treating disease associated with mitochondrialdeficiencies in both humans and animals. This composition can alsoinduce gene expression and activity of T-helper lymphocyte (Th-1)cytokines (e.g., interferon gamma) and can down-regulate T-helperlymphocyte 2 (Th-2) cytokines (e.g., interleukin 13). In addition, itcan inhibit the expression and/or activity of one or more of thefollowing three enzymes: matrix metalloproteinase 1 (MMP1), matrixmetalloproteinase 2 (MMP2), and cyclooxygenase 2 (COX2). It can alsoblock pathways mediated by epidermal growth factor receptor, such asepiregulin-mediated pathways. This composition can be used for enhancingor maintaining physical or mental performance, reducing infection inphysically stressed athletes or non-athletes, and improving immunesystem recovery from intense physical exercises. It also can be anactivator of Sirtuin.

This composition can also be used for treating diseases or disorders,such as a disorder associated with C-reactive protein, autoimmunedisease (e.g., multiple sclerosis, thyroiditis, rheumatoid arthritis,myositis, lupus, or Celiac disease), skin disease (e.g., eczema,urticaria, or psoriasis), lung disease (asthma, pulmonary fibrosis, orchronic obstructive pulmonary disease), prostatitis, arthritis, tumor,diabetes (type II diabetes), sexual dysfunction, chronic constipation,inflammatory disease (e.g., inflammatory bowel disease such as Crohn'sdisease or ulcerative colitis), infection, neurodegenerative disease(e.g., dyslexia, dyspraxia, autism, Asperger's disease, Alzheimer'sdisease, and mild cognitive impairment), and developmental disorder(e.g., attention deficit disorder or attention deficit hyperactivitydisorder); for treating brain injury (e.g., physical damages to thebrain); for improving concentration or mood; for improving the immunesystem, and for lowering blood cholesterol levels or blood pressure. “Adisorder associated with C-reactive protein” refers to any disorder thatresults in an increase in the number of C-reactive protein in blood,such as inflammation or a cardiovascular disorder (e.g.,atherosclerosis, coronary heart disease, stroke, and peripheral arterialdisease). “Tumor” refers to both benign tumor and malignant tumor (e.g.,leukemia, colon cancer, prostate cancer, kidney cancer, liver cancer,breast cancer, or lung cancer). “Infection” includes viral, bacterial,parasitic, and other microbial infection. Examples of viral infectiontreatable by this composition include influenza (e.g., Avian influenzaor infection with influenza A virus subtype H5N1), severe acuterespiratory syndrome (SARS), human immunodeficiency virus (HIV)infection, herpes simplex virus infection, respiratory syncytial virus(RSV) infection, rhinovirus (e.g., human rhinovirus) infection, andcoronavirus infection. The mechanism for treating viral infection bythis composition can include early stage inhibition of viralreproduction by reduction of viral RNA or DNA (e.g., by inhibition oftranscription, reverse transcription, and translation). Bacterialinfection include infection by either gram+ or gram− bacteria andinfection by either anaerobic or aerobic bacteria. Examples of parasiticinfection include leishmaniasis, malaria, and trypanosoma. Otherexamples of infection include respiratory infection, digestive tractinfection, urinary tract infection, blood infection, and nervous systeminfection.

Further, this composition can be used to treat certain symptoms of theabove-mentioned diseases or disorders. For example, it can be used tolessen certain symptoms of multiple sclerosis, including muscleweakness, wasting of muscles, pain (such as facial pain or pain withoutapparent cause), electrical shock sensation, loss of awareness oflocation of body parts, loss of coordination (such as in speech),shaking when performing fine movements, loss of ability to producerapidly alternating movement (e.g., movement in a rhythm), andshort-term or long term memory loss. As another example, it can be usedto reduce the incidence, severity, and/or duration of cold and flusymptoms. In addition, this composition can also be used as a dietarysupplement to improve the quality of life of a patient. For example, itcan be used to reduce obesity (e.g., as a part a weight managementplan), slow the aging process, enhance innate immunity, and improve skinhealth, sexual performance, and digestion.

In addition, this composition can be used to lessen negative sideeffects caused by chemotherapy with drugs such as glivec, taxol, andtamoxifen. It also can be used as an energy booster for patients in needthereof, e.g., cancer patients or AIDS patients. Moreover, it is usefulin enhancing athletic performance for both humans and animals, e.g.,horses.

The terms “improving,” “enhancing,” “treating,” and “lowering” refer tothe administration of an effective amount of a composition of theinvention to a subject, who needs to improve one or more of theabove-mentioned conditions or has one or more of the just-mentioneddisorders, or a symptom or a predisposition of one of more of thedisorders or conditions, with the purpose to improve one or more ofthese conditions, or to prevent, cure, alleviate, relieve, remedy, orameliorate one or more of these disorders, or the symptoms or thepredispositions of one or more of them. The term “administration” coversoral or parenteral delivery to a subject a composition of the inventionin any suitable form, e.g., food product, beverage, tablet, capsule,suspension, and solution. The term “parenteral” refers to subcutaneous,intracutaneous, intravenous, intramuscular, intraarticular,intraarterial, intrasynovial, intrasternal, intrathecal, intralesional,and intracranial injection, as well as various infusion techniques. An“effective amount” refers to a dose of the composition that issufficient to provide a physical benefit (e.g., improving endurance) ora therapeutic benefit (e.g., lowering cholesterol or C-reactive proteinlevels, or reducing the risk of atherosclerosis or heart diseases). Bothin vivo and in vitro studies can be conducted to determine optimaladministration routes and doses.

The compositions described above can be preliminarily screened for theirefficacy in treating the above-described conditions by in vitro assaysand then confirmed by animal experiments and clinic trials. Othersuitable analytical and biological assays are apparent to those ofordinary skill in the art. For example, the bioavailability of quercetincan be measured by conducting pharmacokinetic studies and evaluated bythe area under the curve in a plasma-drug concentration time curve.

Other Embodiments

All of the features disclosed in this specification may be combined inany combination. Each feature disclosed in this specification may bereplaced by an alternative feature serving the same, equivalent, orsimilar purpose. Thus, unless expressly stated otherwise, each featuredisclosed is only an example of a generic series of equivalent orsimilar features.

From the above description, one skilled in the art can easily ascertainthe essential characteristics of the present invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions. Thus, other embodiments are also within the scope of thefollowing claims.

What is claimed is:
 1. A method for treating a disease, loweringcholesterol level or blood pressure, or enhancing mental performance,comprising administering to a subject in need thereof an effectiveamount of a composition containing quercetin, vitamin B3, and vitamin Cas the only active ingredients, a weight ratio between the quercetin,the vitamin B3, and the vitamin C being 1:0.02-1:0.2-2.5; wherein thedisease is multiple sclerosis, thyroiditis, myositis, lupus, celiacdisease, eczema, urticaria, psoriasis, prostatitis, inflammatory boweldisease, arthritis, leukemia, colon cancer, prostate cancer, kidneycancer, liver cancer, breast cancer, lung cancer, sexual dysfunction,chronic constipation, coronary heart disease, atherosclerosis, stroke,or peripheral arterial disease.
 2. The method of claim 1, wherein theweight ratio is 1:0.04:1.
 3. The method of claim 1, wherein the weightratio is 1:0.08:1.
 4. The method of claim 1, wherein the composition isa food product selected from the group consisting of tea, soft drink,juice, milk, coffee, jelly, ice cream, yogurt, cookie, cereal,chocolate, and snack bar.
 5. The method of claim 1, wherein thecomposition is a dietary supplement or a pharmaceutical formulation. 6.The method of claim 1, wherein the vitamin B3 is niacinamide ornicotinic acid.
 7. The method of claim 1, wherein the disease iscoronary heart disease and the vitamin B3 is niacinamide or nicotinicacid.